بسم الله الرحمن الرحيم

The Obesity Pandemic: Where have we

been and Where are we going?

By Amr Abdelmonem,MD.Assistant professor of anesthesia ,surgical intensive care and clinical nutrition in faculty of medicine, Cairo university

Member of North American Association For The Study Of Obesity

Member of the American society of regional anesthesia and pain medicine

The O Word:Obesity

1998, world health organization defined overweight and obesity based on

Body Mass Index ( BMI Kg / m2)Over weight : 25.0 to 29.9

Class 1 obesity: 30.0 to 34.9

Class 2 obesity: 35.0 to 39.9

Class 3 obesity : 40.0 or greater (severely obese)

BMI is not a measure of body compositionBMI is an important correlate of impairedHRQL(health related quality of life)

National institutes of health of the US have recently recommended weight Management based on

Standardized cut- offs for BMI at 25 and 30 Kg/m2

and

On waist circumference ( action levels)Minimum circumference between lower rib margin and iliac crest

Action level 1 at 94 cm in men and 80 cm in womenAction level 2 at 102 cm in men and 88 cm in women•Greater than action level 1 : individuals are at increased health risk ,should avoid weight gain •Greater than action level 2 : are at high health risk ,should seek Professional helpNICK CIRCUMFERENCE measurement is a simple and time-saving screening measure that can be used to identify overweight and obese patients.

Men with NC <37 cm and women with NC <34 cm are not to

be considered overweight

The Pathophysiology of Obesity

• Cultural Influences on Eating and Activity Patterns

• Biologic Factors • Genetic Factors • Effects of Certain Medications • Medical Causes of Obesity

Cultural Influences on Eating and Activity Patterns

• Both leisure and working time are increasingly sedentary as people move from one seated position to another in their use of the automobile, the television, video games, and the computer

The simplistic solution of “’eat less and exercise more’”

does it always work?

Biological factors

Three primary neuroendocrinal components :• Afferent signals (orexigenic and anorexigenic peptides )

• CNS processing unit :VMH-PVN-LHA

• Efferent system :complex of effectors

1. Appetite and its motor component ( medullary NTS)

2. Autonomic nervous system ,with its 2 pathways:

a. sympathetic limb b. parasympathetic limb

3.Three components of total energy expenditure

a. Resting energy expentiture (50 to 65% )

b. Thermal effect of food

c. Voluntary energy expentiture

Afferent signals

Orixegenic peptides

Ghrelin NPY

VMH AGRPVMH

Orexin A-B LHA

Anorexigenic peptides

leptin UCPsCholecyto

kinnin

Ghrelin H does not influence gastric Empyting in obese subjects

Maria E,et al.Obes Res.2005;13:739

Cummings et al.showed that ghrelin rise preprandiallyAnd fall postprandially in healthy subjects

Diabetes 2001;50:1714

In obese subjects ,lower preprandially And higher postprandially

Shiiya T,et al. J Clin Endocrin Metab.2002;87:240

Nobel prize winner Yalow demonstratedThe effect of cholecystokinnin as a Neurotransmitter acting on the Hypothalamus and on the vagus nerve Inviting the sense of fullness

Central processing unit

Location

Ventromedial hypothalamus [VMH;consisting of ventromedial

And arcuate nuclei], Para ventricular nucleus [PVN] and Lateral Hypothalamus [LHA]

Damage to the CPU: hypothalamic obesity

Hypothalamic damage from a tumor, surgery , or radiation results in unrelenting weight gain that is not amenable to diet regimens

However ,not all patients with HO suffer from hyperphagia!!

Efferent system

1.Appetite

• Bridge between energy intake and energy expenditure • Divided into 3 components

[Hunger –Satiation – Satiety]

• Biomarkers [glucose – ghrelin- cholecystokinnin-meal size and

components - vagus n- GLP1-leptin –others]

• Afferent pathways(biomarkers) + efferents from VMH and LHA all meet within NTS

(central integrator that determines satiety versus appetite)

2.Autonomic nervous system

1.Sympathetic nervous system (SNS) Stimulation of the adrenergic beta 3 receptors in

adipocytes ➞lipolysis

2. Parasympathetic nervous system (PNS)Activation of muscarinic M3 receptors

➞acetylcholine ➞ depolarization of beta cell ➞calcium influx ➞ hyperinsulinemia

3.Components of energy expenditure

1. Resting energy expenditure [50-65%of total daily EE]Determined by fat free mass(60-80% variability)Developmental regression of RMR(↑muscle-organ ratio)79.2kcal/Kg 0-2.5 years-36kcal/Kg4-7 years-28.3kcal/Kg

during adolescence-21kcal/Kg in adulthood)◎fat mass-age-sex-physical activity can affect RMR

2.Thermal effect of food [10% of total daily EE]The thermal effect is higher for protein and CHO than for

fat

3. Voluntary energy expenditure [5-50%of total daily EE]• Non-exercise Associated Thermogenesis [NEAT](30% of TEE)(involuntary muscle contraction)• Volitional physical activity !!!

Genetic Factors

• The human obesity gene map 2003 update identified more than 430 gene mutation affecting BMI, body –fat mass ,percentage of body fat ,abdominal fat ,fat-free mass , skin folds , RMR and neuroendocrinal components of energy balance

The world of lipid

Lipid metabolism

Lipids

1. Triglycerides (neutral fat)2. Phospholipids 3. Cholesterol 4. Few others less important

Transportation of lipids

Triglycerides fat globules

Bile

Emulsified fat

Pancreatic lipase

Fatty acids and 2-monoglycerides

Resynthesis

TriglyceridesAggregate

Chylomicrons Thoracic duct

Venous system

Chylomicrons in the venous blood

Capillaries of liver and adipose tissue

Lipoprotein lipase

Hydrolysis of triglycerides

Fatty acids +glycerol

Fat cells

TriglyceridesResynthesis

Release of fat from fat cells

Hydrolysis of triglycerides

into FA + glycerol by

1. Low carbohydrate load to fat cells 2. Hormone sensitive lipase (HSL)

On leaving fat cells ➞ FA ionize in the plasma ➞ immediately combines with albumin molecules (FFA)

Free fatty acid (FFA )

• Concentration of FFA in the plasma during resting conditions is 15mg/ dl of total FA of .5gm

• This small amount is the physiologically active because:

1. Every 2-3 minutes half of the plasma FFA is replased with new FA

◎almost all energy requirements of the body can be provided by oxidation of the transported FFA without using CHO or proteins

2. All the conditions that increase the rate of FA utilization also increase FFA conc up to 5 to 8 folds

The Fat Depots

• Large quantities of fat are stored in 2 major

tissues Adipose tissue and liver

Adipose tissue is called fat depots

Adipose Tissue vs. Fat

Age Males Females

10-30 12-18 20-26

31-40 13-19 21-27

41-50 14-20 22-28

51-60 16-20 22-30

61 17-21 22-31

Total body adipose tissue percentage

Traditional Adipose Tissue Classification

• Classical anatomy was mainly organ-centered, without recognizing the specialized organ-like functions of different tissues

• This was especially true of adipose tissue, which only recently has been recognized as an "endocrine organ “

N Engl J Med .2001;345:1345

• Simple anatomic adipose tissue groupings :subcutaneous adipose tissue, organ-surrounding adipose tissue, interstitial adipose and adipose tissue in bone marrow

• Adipose tissue is also named according to special biological functions, such as white, mammary gland, brown, and bone marrow adipose tissues

Recent proposed Classification of total body adipose tissue

Shen et al,Obes Res.2003;11:1

Subcutaneous

Superficial

Deep

Internal

Visceral Non- visceral

Intrathoracic

Intrapricardial

Extrapricardial

Intraabdominopelvic

Intraperitoneal Extrapritoneal

Preperitoneal Retrroperitoneal

Intraabdominal Intrapelvic

ParametrialRetropubicParavesical

Retrouterine Pararectal Retrorectal

IntramuscularPerimuscular

Orbital

Dynamic state of storage fat

• Exchange of fat between adipose tissue and blood :

Because of rapid exchange of FFA

Triglycerides in the fat cells are renewed approximately once every 2 to 3 weeks

Use of triglycerides for energy

1. Hydrolysis of triglycerides ➞ FA + glycerol

2. Entry of FA into mitochondria by carnitine shuttle system

3. Splitting of acetyl CoA from FA4. Oxidation of acetyl CoA in citric acid

cycle

The liver lipids

The principal functions of liver in lipid metabolism

• Degradation of fatty acids • Synthesize triglycerides from

carbohydrates • Synthesize other lipids (cholesterol and

phospholipids )

Formation of acetoacetic acid in the liver

• Large share in the initial degradation of FA• FA➞ acetyl CoA ➞ 2 acetyl CoA + H2O

➞acetoacetic acid ➞ other cells for energy

• Acetoacetic acid can also be converted to B-hydroxybuteric acid and acetone

• Acetoacetic acid and B-hydroxybuteric acid diffuses through liver cell membranes to blood to other tissues for energy

• Their transport is so rapid not more than 3 mg/dl except in!

Ketosis

• The name acetoacetic acid consist of keto acid and 3 compounds called ketone bodies

• Excess FA ➞ excess acetoacetic acid ➞ ketosis

• Low carbohydrate load (DM,starvation or high fat diet)

• Tremendous quantities of FA become available to liver for degradation ➞ excess keto acid and ketone bodies

Synthesis of triglycerides from carbohydrates • CHO either used for energy or stored as

glycogen

• However excess CHO will be converted to triglycerides (liver) to be trasported by VLDL to adipose tissue

• Average person has almost 150 times as much energy stored in the form of fat as stored in the form of CHO

• Each gram of fat gives 2.5 times calories as CHO

Fat sparing effect of carbohydrates

• Excess of carbohydrates ➞ preffered metabolic fuel because :

1. ↑α-glycerophosophate ➞shift metabolism toward fat storage

2. FA synthesized more rapidly than they are degraded because of the availabilty of acetyl CoA carboxylase ➞ converts acetyl CoA to FA

◎excess CHO in diet not only spares fat but also increases fat synthesis

Upper and Lower Body Adipose Tissue Function: A Direct Comparison of Fat Mobilization in males between 22 to 43years. Garry .Obes Res,2004

• Objectives:

Fat in the lower body is not associated with the same risk of cardiovascular disease as fat in the upper body.

Is this explained by differences in the physiological functioning of the two depots? This study had two objectives:

1) to determine whether fat mobilization and blood flow differ between gluteal and abdominal adipose tissues in humans, and

2) to develop a new technique to assess gluteal adipose tissue function directly.

• Research Methods and Procedures:

They performed detailed in vivo studies of

adipose tissue function involving the assessment of fat mobilization by measurement of adipose tissue blood flows, arterio-venous differences of metabolites across each depot, and gene expression in tissue biopsies in a small-scale physiological study.

• Results:

Gluteal adipose tissue has a lower blood flow (67% lower, p < 0.05) and lower hormone-sensitive lipase rate of action (87% lower, p < 0.05) than abdominal adipose tissue. Lipoprotein lipase rate of action and mRNA expression are not different between the depots.

This was the first demonstration of a novel technique to directly investigate gluteal adipose tissue metabolism.

Discussion

Direct assessment of fasting adipose tissue metabolism in defined depots show that the buttock is metabolically "silent" in terms of fatty acid release compared with the abdomen.

Another study done by Dora B and his colleagues demonstrated that :

1. Abdominal adipocytes are more sensitive and responsive to beta adrenergic stimulation of lipolysis than gluteal adipocytes

2. Gluteal lipocytes have higher LPL activity than abdominal lipocytes

This study was done on post menopausal femalesDora B, et al. regulation of lipolysis and lipoprotein lipase after weight loss in obese ,postmenopausal women .Obes Res .2004;12:32

Metabolic syndrome

What is metabolic syndrome?

• Metabolic syndrome is a collection of health risks that increase the chance of developing heart disease, stroke, and diabetes.

• The condition is also known by other names including Syndrome X, insulin resistance syndrome, and dysmetabolic syndrome.

What are these health risks?ATP III Guidelines WHO Guidelines

Abdominal Obesity 

Waist Circumference Waist/Hip Ratio Men > 40 inches (102 CM)  >0.90 Women > 35 inches (88 CM)  >0.85

Other Variables Triglycerides 150 mg/dL 150 mg/dLHDL-Cholesterol Men < 40 mg/dL <35 mg/dL Women < 50 mg/dL <39 mg/dLBlood Pressure 130/ 85 mm Hg >140/>90 mm HgFasting Glucose 110 mg/dL 110 mg/dLWHO guidelines also include microalbuminuria (>20 µg/min or albumin:creatinine ratio >30 mg/g).

The pathogenesis of metabolic syndrome

Complex interplay of a still largely unknown genetic background with environmental lifestyle- related factors

Environmental lifestyle-related factors:

When we eat ,our bodies break down the food into its basic components ( protein- carbohydrates- fat), and absorbs them into blood stream rise in blood sugar pancreas will release insulin moves sugar into cells either burned for energy or stored away as fat in fat cells or glycogen in liver and muscles

Years of dietery abuse in susceptible patients malfunctioning of insulin sensors hyperinsulinemia

Continued dietery abuse insulin sensors to sluggish insulin resistance

Markers of insulin resistance :

Hypertriglyceridemia

HDL

Hypertension

Hyperinsulinemia (>15µu/ml) Marc C,et al. Obes Res.2005;13:703

Abdominal obesity

Hyperglycemia

Marjo etal , proven liver fat accumulation as an important marker Obes Res 2002; 10: 859

Obesity Lets walk through the fat metabolism pathway and follow the flow of fat molecules:

Fat travels in the form of triglycerides at cells ezymatic breakdowen fatty acids enter the cells mitochondria breakdowen fat in order to enter mitochondria ,fats need carnitine

insulin inhibitsFat- carnitine shuttle system fats move back into blood

Glucagon accelerates this shuttle system

Muscle ,liver, kidney, lung, heart and other cells break down fat

Two enzyme systems on the surface of fat cells regulated by insulin and glucagon

Insulin stimulates lipoprotein lipase that transports fatty acid into fat cells

Glucagon stimulates hormone sensitive lipase that releases the fat from fat cells into the blood

Although we cannot control lipoprotein lipase directly, we can control It indirectly by cotrolling the metabolic hormones ,insulin and glucagon

Fat cells merely store the fat molecules !

Functions of Cholesterol :• Adrenal hormones and sex hormones• Main component of bile acids• Essential for normal growth and development of

brain and nervous tissue• Gives the ability of skin to shed water • Precursor of vitamine D3 in the skin• Normal growth and repair of tissues• Transportation of triglycerides

DYSLIPIDEMIA

Where does cholesterol come from?

80 % comes from the body itself , every cell in the body is capable of making its own cholesterol , most don’t and rely instead on that made in the liver and skin.

Cholesterol and triglycerides are insoluble in blood

Lipoproteins are envelops that enclose cholesterol and triglycerides Making them soluble in blood,so that they can be transported to tissues

Sequence of events in the life of lipoproteins

Liver Makes and release VLDL

TRIGLYCERIDES WITH CHOLESTEROL

TRI AND CHOLES MATUREVLDL

TriglyceridesReleased to bloodAnd tissues

CholesterolBulk +tri LDL

HDL

Scavenges cholesterlFrom tissues carriesThrough bloodHands it off to

VLDL

More triglycerides release

Removed by liver

CholesteroLrich

LDL

Released to tissuesDeposited in coronary arteries

When the level of cholesterol inside the cells falls LDL receptors Attach to the surfaces of the hepatic cells invaginate LDL cholesterol By endocytosis

Obese patients with insulin resistance have LDL receptors dysfunction

Cholesterol synthesis inside the cells depends on an enzyme named3- hydroxy-3 methyl-glutaryl-coenzyme A reductase

Couple of hormones affect the activity of the rate limiting enzymeHMG-CoA reductase

INSULIN AND GLUCAGON

Hypertension

Data from NHANES III show that the (age – adjusted prevalence) Of high blood pressure increases progressively with higher levels Of BMI in men and women

High blood pressure is defined as

SBP 140 mm Hg or MBP 90 mm Hg or currently taking antihypertensives

What is the etiology that connects obesity and hypertension?

Hyperinsulinemia and insulin resistance

Mechanism

1. Increased sodium retention

1. Increased sympathetic nervous system activity

1. Alteration in the mechanics of blood vessels

However

It is known that weight loss is associated with

vascular resistance,total blood volume and cardiac output

•Improvement in hyperinsulinemia and insulin resistance

• sympathetic nervous system activity

•Suppression of the activity of renin angiotensin aldosterone system

•Recently ,serum angiotensin converting enzyme activity declines with modest weight loss.

The precise mechanism whereby weight loss

results in a decrease in Blood pressure is unknown .

Type II Diabetes mellitus

• It represents 90% of all cases of diabetes.• Requires years of underlying metabolic

disturbance before symptoms become apparent

• The development and diagnosis usually follows weight gain

• In Type I and Type II diabetes blood sugar is elevated but for different reasons

•Type I there is no insulin to hold it down by moving it into cells

•Type II the cells become resistant to insulin that even large amounts cant adequately move the sugar into cells

•In early stages there is hyperinsulinemia ,later pancreatic beta cells wear out from constantly producing insulin under stimulation of hyperglycemia

•Resistin is a protein secreted by fat cells as a signal from adipose tissue linking obesity to insulin resistance and type II diabetes Liese et al, Eur J Nutr.2001;40:282

•Increased White blood cell count is correlated with insulin resistance in diabetic obese females

Pannacciulli et al,Obes Res.2003;11:1232

Coronary artery disease • Observational studies have shown that

overweight,obesity, and VAT are directly related to cardiovascular risk factors

( cholesterol , LDL, triglycerides, hypertension, fibrinogen,hyperinsulinemia , HDL, plasminogen activator inhibitor )

RECENTLYComplement 3 and acute phase proteins is the immunological link between central obesity and CHD

The term "Syndrome X" refers to a heart condition where chest pain and electrocardiographic changes that suggest ischemic heart disease are present, but where there are no angiographic findings of coronary disease.

•Recent studies have shown that risks of nonfatal myocardial infarction and CHD death increase with increasing levels of BMI

•In British, Swedish, Japanese and US populations , CHD incidence increased at BMIs above 22 and an increase of 1 BMI unit was associated with 10 % increase in the rate of coronary events

•Recent study has found that obese CHD patients are younger and and are hospitalized more frequently during the first 10 years of their illness than the non-obese

Obesity and cardiac dysrhythmias(prolonged Q-T interval)

• Q-T interval is usually measured in lead II , and is corrected for heart rate .

• Q-Tc= measured Q-T square root of R-R interval• Prolonged Q-T interval reflects prolonged

repolarization of the ventricle• Proposed mechanism is increased SNS activity• Recent study had found that Prolonged Q-T

interval is associated with abnormal WHR ,higher levels of FFA and hyperinsulinemia in obese women .

• Wight loss leads to normalization of Q-Tc with attenuation of hyperinsulinemia

Esposito et al,Obes Res.2003;11:653-659

Oxidant Stress

Imbalance

Between

Formation Of Reactive oxygen/nitrogen species (ROS/RNS)

And Antioxidants

Pathologic stress Induces monocytes to release mediators

(TNF and interleukins 1-6-8) Activates PMNs

Release ROS(superoxide (O2·-), hydrogen

peroxide, hypochlorite, nitric oxide (NO), hydroxyl radical

Induce tissue injury by:1. damaging DNA2. Cross linking cellular proteins3. Peroxidation of membrane lipids • Diminishing membrane fluidity• Increasing membrane permeability

Oxidant Stress and Obesity

•Adipocytes and preadipocytes have been identified as sources of inflammatory cytokines:

including TNF , interleukin (IL)1-ß, and IL-6.

•Stimuli capable of inducing cytokine release from adipocytes may include:

lipopolysaccharides, intracellular triglycerides, and catecholamines

http://www.obesityresearch.org/cgi/content/full/10/9/964/F2

We could predict that:

•The accumulation of intracellular triglycerides or tissue adiposity promotes increased oxidant stress

•Therefore reduction of total body fat through diet and/or exercise may be an effective means of reducing systemic inflammation and oxidant stress.

Consistent with this prediction

Reductions in plasma markers of oxidant stress and in ROS generation by isolated leukocytes have been observed after 4 weeks of energy restriction and weight loss.

Dandona et al. J Clin Endocrinol Metab,2001; 86:355-363

Good news

Physical activity •Decreases adipose derived inflammatory mediators •Activates signaling pathways that lead to increased synthesis of intracellular antioxidants and antioxidant enzymes and decreased ROS production Miyazaki et al, Eur Appl Physiol.2001; 84:1-6 Pischon et al, Obes Res.2003;11:1055

A novel pathway to the manifestations of metabolic syndrome(2004)

Obesity And Diseases

Obesity and cancer

• Strong risk factor for esophageal cancer

• Uterine and gall bladder cancer in obese women

• High risk for colon and prostate cancer in obese males

• Breast cancer for obese postmenopausal women

What is the link between obesity and cancer

1. Hyperinsulinemia and insulin resistance

2. Oxidant stress

Obesity and osteoarthritis

• Degenerative process affecting articular cartilage• Predisposing factors: advancing age + genetic

predisposition + obesity• Common affected sites :knees and hips then cervical

spine and lower lumbar area• Pathogenesis :• Forces across the hip and knee during walking and stair

climbing are 2 to 4 times normal body weight and each extra weight will multiply these forces on the joints

• NHNES showed that adults with BMI>30 have 4 folds higher prevalence than those <30

• Leptin overexpression in arthritic joint is related to cartilage destruction and correlated with BMI

Obesity and gout• Is a metabolic disorder of purine metabolism

• Either primary :genetic defect in purine metabolism

Or secondary to: chemotherapeutic drugs, renal impairment , thiazide diuretics ,alcohol abuse and purine rich foods (liver,kidney,peas,lentils,red meat)

• Clinical picture :crystals of uric acid (tophi) build up forming large deposits in : metatarsophalyngeal joints, wrist,elbow,knee,and extraarticular tissues(nephrolithiasis, myocardium, aortic valve and extradural spinal region.

• Recently :insulin resistance is the precursor of gout (journal of american medical association

• Diet regimens that lead to gout: any regimen that results in a rapid weight loss will increase uric acid 2-3 folds)

Obesity and gallstones

• The incidence of gallstones is significantly higher in obese women and men

• The risk of stone formation is also high if a person loses weight too quickly

Obesity and lungs

• Increased risk of intrapulmonary shunts and ventilation perfusion mismatching

• Pickwickian syndrome

Obesity and sleep apnea and sleep disorders

• Obese tend to fall asleep faster and sleep longer during the day

• At night ,it takes them longer to fall asleep they sleep less than others.

• When the upper airways relaxes and collapses at intervals during sleep ,thereby temporary blocking the passage of air (sleep apnea)

• Symptoms :morning headach, fatigue and irritability

• Side effects :dysrhythmias,stroke ,right sided heart failure and car accidents

• Sleep apnea deprives patients from REM sleep• REM sleep: the dreaming phase of sleep,

necessry for emotional wellbeing• Obesity leads to sleep apnea which leads to loss

of REM sleep which leads to raising of BMI

OBESITY AND EATING DISORDERS

• Binge eating : about 30% of obese are binge eaters ,who typically consume 5000 to 15000 calories in one sitting

• To be diagnosed as a binge eater ,person has to binge twice a week for 6 months

• Bulimia : binge eating followed by purging in order to lose weight

• Anorexia : severe weight loss and is life threatening

Types and approaches to obesity treatment

1. Do it yourself programs

2. Non-clinical programs

3. Clinical programs • Individual heath care professional

• Multidisciplinary group of professionals (physician ,dietitian ,exercise and psychological counselors )

Evaluation of the program by the physician

• The match between the program and the consumers• The soundness and safety of the program:1. Assessment of physical health and psychological status

2. Attention to diet and pharmacotherapy

3. Attention to physical activity

4. Program safety

• Outcome of the program

1. Long-term weight loss

2. Improvement in obesity related co morbidities

3. Improved heath practice

4. Monitoring adverse effects that might result from the program

Caloric restriction• Normal caloric intake 20-25 calories for each Kg

of the body weight or

• According to Harris-Benedict equation: for males RMR= 66.4+ 13.8 W + 5H – 6.8A for females RMR= 665+ 9.6W+ 1.8H – 4.7AW=weight (kg), H = height (cm), and A= age (yr)e.g. weight : 120 kg H= 175 A=35RMR= 66.4 + 13.8(120)+5(175) – 6.8(35)=2359.5

• Less than 500 calories deficit per day➞ weight loss of .5 Kg per week

Side effects of very low caloric diets < RMR • Increase NPY• Rebound effect ( leptin)

• Insufficient vitamines (ADEK) and minerals (Ca,zinc,iron and folic acid)

• Fatigue ,intolerance to cold,hair loss, gall stone formation ,gout , and menstrual irregularities

• Hypokalemia due to diuresis ➞arrhythmias

• Hypernatremia ➞ fatigue, dizziness , confusion and coma

• Constipation (absence of insoluble fibres)

Glycemic Index• In 1981 Jenkins and his collegues developed the

GI. • The GI for a food was defined relative to a

standard food (glucose or white bread). • Over a 2-hour period, the area under the

glucose response curve after consuming 50 grams of carbohydrate from the test food was compared with the area under the glucose response curve after consuming 50 grams of carbohydrate from the reference food.

• Both levels were given as the difference from fasting blood glucose levels .

• The tests have been done in both healthy people and people with diabetes.

Jenkins and his colleagues have proposed that

• All carbohydrates are not equivalent and that the rate of absorption of carbohydrate foods into the bloodstream is a critical factor in hyperinsulinemia.

• Slowly absorbed foods would be beneficial because they trigger less of a rise and fall in blood glucose and, thus, less of a rise and fall in insulin levels

Supportive researches• The Food and Agriculture Organization of the United

Nations and the World Health Organization have issued an extensive report on various aspects of carbohydrate in the diet that endorsed using the GI as an appropriate guide for preventing obesity (1998)

• Other organizations have followed suit, particularly in Europe (1998) , Canada, and Australia (2002) ..

• Writing in support of statements from the European Association for the Study of Diabetes, Ha and Lean (1998) have endorsed the use of the GI as one method of assuring that carbohydrate foods with slower absorption times be encouraged to assist in glycemic control.

• In the U.S., Bell and Sears (2003) have similarly encouraged the use of the GI to create a diet that features low-GI carbohydrates as a way of reducing the rising levels of both obesity and type 2 diabetes in the U.S.

The Glycemic load

• Definition :The GI multiplied by the grams of carbohydrate in a specific portion of a carbohydrate-containing food.

• Because it slows absorption and lessens hyperinsulinemia, a low–glycemic-load diet would promote appropriate weight loss, improve cardiovascular health, and reduce diabetes

• e.g., Carrots illustrate the leveling effect of using glycemic load • it has a high glycemic index, but because it contains relatively

little carbohydrate, it ends up with a modest glycemic load Salmeron, J, Manson, JE, Stampfer, MJ, Colditz, GA, Wing, AL, Willett, WC. (1997) Dietary fiber, glycemic load, and the risk of non-insulin-dependent

diabetes mellitus in women JAMA 277,472-477

Bell, SJ, Sears, B. (2003) Low-glycemic-load diets: impact on obesity and chronic diseases Crit Rev Food Sci Nutr. 43,357-377

Alternative food pyramidLudwig, DS. (2000) Dietary glycemic index and obesity J Nutr. 130,280S-283S

• Ludwig in 2000 has developed an alternative food pyramid based on the GI.

• The base (low-GI foods) is vegetables and fruits

• The second tier is reduced-fat dairy, lean protein, nuts, and legumes

• The third tier is unrefined grains and pasta

• and the top level, which should be the most restricted in diet planning, is refined grains, potatoes, and sweets.

Obstetric and Pediatric studiesBrand-Miller, JC, Holt, SHA, Pawlak, DB, McMillan, J. (2002) Glycemic index and obesity Am J Clin

Nutr. 76(suppl),281S-285S • Weight gain was also lessened with a low-

GI diet in a small study (n = 12) of pregnant women.

• In a retrospective pediatric study, greater weight loss has been seen with a low-GI diet compared with a conventional low-fat diet, although these do not seem to have been isoenergetic diets

A more recent review by Brand-Miller et al. (2003) has reviewed 14 studies of glycemic control in people with diabetes using high- vs. low-GI diets. Although most of the studies were on small numbers of people, and the usual dietary compliance problems in free-living individuals can be assumed, a slight, but significant, benefit in glycemic control with low-GI diets was detected.

Brand-Miller, J, Hayne, S, Petocz, P, Colagiuri, S. (2003) Low-glycemic index diets in the management of diabetes: a

meta-analysis of randomized controlled trials Diabetes Care 25,2261-2267

Criticisms of the GI

• As is immediately apparent from examination of the GI table Foster-Powell, K, Holt, SHA, Brand-Miller, JC. (2002) International table of glycemic index and glycemic load values: 2002 Am J Clin Nutr. 76,5-56 )

• Values for the GI of foods can be rather broad.

• Published GI for boiled white rice, for instance, varied from 45 to 112 .

• Bananas ranged from 30 to 70, partially depending on their degree of ripeness.

• White durum-wheat semolina spaghetti varied from 46 to 65, depending on length of cooking time.

Judwith et al. Obes Res.2004

Energy Density

• Definition Amount of energy in a given weight of food(kcal/g)

• For the same amount of energy ,a greater weight of food can be consumed when the food is low in energy density than when its energy density is high

Barbara j ,et al. J Am Diet Assoc.2005;105:S89

Components that have greatest impact on energy density

1.Water : has the greatest impact because it adds substantial weight without energy

2.Fat :because of its high caloric content (9kcal/g)

! not all high fat foods have high energy density ,water lowers ED even of high fat food e.g., cheese has same ED of fat free but dry pretzels

3.Fiber : modest influence as only limited amount of fibers can be added to food

Researches on energy density

• Studies by Rolls and Bell (2000) have shown that people often select food quantity by weight, so that when low-energy-dense foods are selected, calorie content is often decreased

• More recent work by Rolls et al. (2004) has shown that modifying meals to increase the amounts of fruits and vegetables, which are generally not particularly energy dense, increases satiety and leads people to select meals with a lower total calorie content

• However, they have also found that instructing subjects to increase the fruits and vegetables in their diet was not sufficient for weight loss to occur, unless the added fruits and vegetables also displaced high-energy-dense foods

American Society for Clinical Nutrition, has noted that a number of diet strategies exist for weight loss and that different individuals may find different strategies useful. Although they do not specifically endorse either the GI or energy density as methods for choosing foods, they have noted that both have some support in the literature and that further research into them is warranted Klein, S, Sheard, NF, Pi-Sunyer, X, et al (2004) Weight management through lifestyle modification for the prevention and

management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North

American Association for the Study of Obesity, and the American Society for Clinical Nutrition Am J Clin Nutr. 80,257-263

Jeff S,et al.cardiovascular and hormonal aspects of very low Carbohydrate

ketogenic diet.Obes Res.2004;S12:11s5

• The design was a parallel ,randomized ,clinical intervention study of an energy restricted (deficit of 500 kcal/d) CLCKD and low fat diet (< 30%total energy from fat) in 29n healthy over-weight /obese men and premenopausal women for 8 weeks.

VLCD Low Fat Diet

TC -11% -15%

LDL NO CHANGE -18%

HDL -3% -7%

TG -44% -15%

VLCD Low Fat Diet

FAT LOSS -775 g/w -384 g/w

TRUNKAL MASS -505 g/w -157 g/w

INSULIN - 29% -12%

LEPTIN - 50% -17%

FREE T3 No significant changes No significant changes

GLUCAGON No significant changes No significant changes

Inflammation Biomarkers

Same significant reductions

Same significant reductions

REE (kilojoules/Kg)

Not significantly affected

Not significantly affected

Traditionally ,a low fat –high carbohydrate diet has been recommended to help obese patients lose weight

National institute of health ,national heart ,lung and blood institute ,and national institutes of diabetes and digestive and kidney

diseases .clinical guidelines on the identification ,evaluation ,and treatment of overweight and obesity in

adults .Bethesda,MD:NIH;1998

Data from a recent meta analysis that evaluated randomized clinical trials that compared fat-restricted and calorie restricted diets has found no difference in weight loss between diet groupsPirozzo S,etal.Cochrane Database Syst Rev.2002;2:Cd003640

The results from four randomized controlled trials that compared the effect of low carbohydrate diet with a low fat diet on body weight in adult obese subjects have recently been published

Brehm, et al . (2003) A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women J Clin Endocrinol Metab. 88,1617-1623

Samaha, et al (2003) A low-carbohydrate as compared with a low-fat diet in severe obesity N Engl J Med. 348,2074-2081

Foster, et al (2003) A randomized trial of a low-carbohydrate diet for obesity N Engl J Med. 348,2082-2090 Yancy, WS,et al. (2004) A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and

hyperlipidemia: a randomized, controlled trial Ann Intern Med. 140,769-777 Stern, et al (2004) The effects of low-carbohydrate versus conventional weight loss diets in severely obese

adults: one-year follow up of a randomized trial Ann Intern Med. 140,778-785

• A consistent difference in weight loss at 6 months has been observed between groups across studies; subjects randomized to the low-carbohydrate diet lost 4 to 5 kg more weight than those randomized to the low-fat diet.

• However, weight loss was no different between groups at 1 year .

• In addition, in subjects who had type 2 diabetes, there were greater improvements in fasting blood glucose concentrations and insulin sensitivity with a low-carbohydrate than with a low-fat diet.

• The data from these studies has also found greater improvements in serum triglyceride and high-density lipoprotein-cholesterol concentrations,

• but not in serum low-density lipoprotein-cholesterol concentrations, in the low-carbohydrate than the low-fat group .

Mitochondrial uncouplings

All UCPs may lower mitochondrial ATP production through respiratory uncoupling ,thus stimulating substrate oxidation in mitochondria

Ricquier D, etal. Biochem J.2000;345:161- Fink BD,etal. J Biol Chem.2002;277:3918

In transgenic mice ,high fat diet stimulates respiratory uncoupling in white adipose tissue and may lower plasma lipids by inducing fat oxidation .

Martin R,etal.Obes Res.2005;13:835.

• At present, it is unlikely that one diet is optimal for all overweight or obese persons, and dietary guidance should be individualized to allow for specific food preferences and individual approaches to reducing weight.

• Walking is metabolically expensive for obese :

1. Greater body mass and heavier legs

2. Decreased stability and wider lateral leg swing.

Energy cost of walking is 20-100%greater for obese

• Walking slower for a set distance is an appropriate exercise recommendation for weight management prescription in obese adults

Raymond ,etal. Obes Res .2005;13:891

Why treat overweight and obesity?

Not only to improve the BODY IMAGE But also to reduce the OBESITY –RELATED COMORBIDITIES